Abstract Among the 6 racial and ethnic categories recognized by the US Census Bureau, 3 stand out for their similarity in history, demographics, visibility, and health: American Indians (AIs), Alaska Natives (ANs), and Native Hawaiians and Pacific Islanders (NHPIs). NHPIs and AI and ANs (the latter 2 are typically combined) are the smallest and second-smallest US racial groups, with populations of 1.2 and 5.2 million, respectively. These groups experience harsh disparities in health and mortality compared to US Whites. Concerning are their population prevalences of hypertension, cardiovascular disease (CVD), and stroke, which are as high as, and usually higher than, US Whites. Despite these serious public health inequities, both groups have been largely neglected by health research. A literature search for interventions targeting blood pressure (BP) control as a contributor to CVD and stroke in AIs, ANs, and NHPIs returned no results. No interventions ? and thus no multilevel intervention studies ? have ever focused on BP control in these groups. Accordingly, the overarching objective of Native-Controlling Hypertension And Risks through Technology (Native-CHART) is to improve control of BP and associated CVD and stroke risk factors among these populations. Our research agenda articulates a practical model of health and health disparities grounded in lived experience as well as in theory. Our community-based participatory approach increases the likelihood that findings will confer sustainable benefits within AI, AN, and NHPI communities, which range from large urban areas to frontier villages in Alaska. Our approach harnesses technologies available in the settings where participants live, work, and obtain healthcare ? including electronic health records, text messaging, online grocery shopping apps, wearable physical activity monitors, and home BP monitors. Our 3 Research Projects feature interventions at the individual, family, community, and policy levels. Our Specific Aims are to: 1) expand and establish new collaborations with research partners across private, tribal, and public constituencies that address BP control within a multilevel intervention framework; 2) develop a multilevel, multisector infrastructure that ensures inclusion of local, regional, and national views on research priorities and approaches to controlling BP; 3) promote a scientifically rigorous, culturally informed program of inquiry that acquires new knowledge to implement innovative approaches to increase hypertension knowledge and awareness, activate patients, increase medication adherence, and improve BP control among AIs, ANs, and NHPIs. Our goal is to move research on BP control and CVD and stroke risk factors in these communities beyond its current, largely descriptive state, and translate that knowledge into meaningful action.